Sciencemadness Discussion Board - Ideas needed - Oxiation of acid sensitive asarone to 2,4,5-trimethoxybenzaldehyde

Ideas needed - Oxiation of acid sensitive asarone to 2,4,5-trimethoxybenzaldehyde

Methansaeuretier - 20-6-2010 at 21:32

Hello,
I try to make 2,4,5-trimethoxybenzaldehyde via oxidation of asarone. The yields with KMno4/NaHCO3 are pretty bad (about 25 %) because it's oxidised further to the corresponding acid and dichromate/H2SO4 gave also miniscule yields because asarone is very sensitive to acid.

I've read in a german chemistry forum that it's possible to oxidise isoeugenol to vanillin using nitrobenzene, but poorly I can't find any reference.
(http://www.chemieonline.de/forum/showthread.php?t=125945)

Is it possible to use dichromate without H2SO4?

Any ideas?

zed - 20-6-2010 at 22:23

Well, direct nitration of Asarone via Tetranitromethane, might produce the Nitropropenylbenzene, then.... refuxing with N-methylbenzylamine, might produce the schiffs base of the benzaldehyde.....Plus a fair amount of Nitroethane as gas.

Shulgin advocates the procedure for production of the rare myristicin aldehyde.
The drawback being, that tetranitromethane, which is fairly easy to make, is quite difficult to handle. Highly explosive.

Another approach, and the preferred one, from an industrial standpoint, would be ozonolysis. Ozone cleaves propenylbenzenes to produce benzaldehydes....With super high yields. Thereby, the common Eugenol, becomes (the rare in nature) Vaniilin.

There are multiple, though somewhat unreliable, postings on this subject elsewhere. Consult the Rhodium Archive, generously maintained by The Vaults of Erowid. While you are visiting, Erowid would appreciate a donation.

http://www.erowid.org/archive/rhodium/

Some folks say negative things about The Vaults, but they provide a good service. What other site provides such truthful, personal, psychedelic accounts?

http://www.erowid.org/experiences/exp.php?ID=19572

http://www.erowid.org/experiences/exp.php?ID=3598

[Edited on 21-6-2010 by zed]

[Edited on 21-6-2010 by zed]

[Edited on 21-6-2010 by zed]

[Edited on 22-6-2010 by zed]

Methansaeuretier - 20-6-2010 at 22:51

Thank you
Both ways are very unpractical for me... at least the tetranitromethane-way doesn't sound like fun und the ozone-way sounds like very long reaction times and a mess of side reactions, because you can't get enough clean ozone with an UV-C lamp or something similar and O2 does also oxidise the aldehyde further to the corresponding acid during long reaction time.

What about Dichromates in non- or only slightly acidic, buffered or maybe weak alkali solutions?

BTW:
I found something interesting about the nitrobenzene-way:
http://www.lycaeum.org/rhodium/pdf/aromatic.aldehyde.synthes... on Page 237

Quote:

By treating nitrotoluenes with either a solution of alcoholic-aqueous sodium sulfide, a solution of sulfur in concentrated alcoholic-aqueous sodium hydroxide, or fuming sulfuric acid, oxidation and reduction within the same molecule Tdl occur and produce aminobenzaldehydes and aminonaphthaldehydes in yields up to 70 per cent (16,101, 194,263). Occasionally aldehydes are not produced and sometimes toluidines and aminobenzoic acids are formed as the main products; hence the method is not general (271).

Sounds very nice, but poorly I can't finde any ratios or further instructions.

[Edited on 21-6-2010 by Methansaeuretier]

not_important - 20-6-2010 at 23:04

besides ozone

http://www.sciencemadness.org/talk/viewthread.php?tid=6914

with a phosphate buffer added after formation of the peracid and before the substrate.

Arrhenius - 21-6-2010 at 00:02

How about epoxidation with your favorite reagent - I'll pick mCPBA. Then hydrolyze to the glycol with an acid - I'll choose perchloric because I know it works fantastic. Next cleave the glycol - I'll choose periodate because I favor my life over Pb(OAc)4. Two side products may be the a rearrangement of the epoxide to the acetophenone or benzyl ketone.

P.S. Ozone will not give you the benzoic acid - not to mention it would be easily freed of acidic side products. See the Criegee Intermediate and secondary ozonide here here. The aldehyde is liberated upon reduction of the secondary ozonide with dimethylsulfide or thiourea. But yes, long reaction times will eventually rip the benzene ring to shreds.

I have no idea what you're getting at with "what about dichromates"

Methansaeuretier - 21-6-2010 at 00:44

Quote: Originally posted by Arrhenius

How about epoxidation with your favorite reagent - I'll pick mCPBA. Then hydrolyze to the glycol with an acid - I'll choose perchloric because I know it works fantastic. Next cleave the glycol - I'll choose periodate because I favor my life over Pb(OAc)4. Two side products may be the a rearrangement of the epoxide to the acetophenone or benzyl ketone.

Would'nt that mostly produce (in theory) phyenylacetone? All I want is the benzaldehyde, I'm not planning to make the amphetamine :mad:

forget your dirty thoughts!

BTW I think in practice major product of working with these acids would be that:

Even if you would isolate some epoxide, the rearrangement may produce similar pain. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi...

Quote:

P.S. Ozone will not give you the benzoic acid - not to mention it would be easily freed of acidic side products. See the Criegee Intermediate and secondary ozonide here here. The aldehyde is liberated upon reduction of the secondary ozonide with dimethylsulfide or thiourea. But yes, long reaction times will eventually rip the benzene ring to shreds.

Thank you. May a 1000mg/h ozone generator work for this?

[Edited on 21-6-2010 by Methansaeuretier]

Nicodem - 21-6-2010 at 01:15

Quote: Originally posted by Methansaeuretier

Quote: Originally posted by Arrhenius

Would'nt that mostly produce (in theory) phyenylacetone? All I want is the benzaldehyde, I'm not planning to make the amphetamine :mad:

forget your dirty thoughts!

Oxidative cleavage of that glycol with metaperiodate gives the corresponding benzaldehyde (and not arylacetone as you seem to believe). Essentially, what Arrhenius proposed, is to prepare the glycol in separate steps followed by the usual oxidative cleavage with NaIO4 instead of doing the oxidation to the glycol and the cleavage to 2,4,5-trimethoxybenzaldehyde in one step like it is usually done (and requires OsO4 catalysis like in Chemistry Letters, 32, 780-781 or WO2002079132). This way you avoid the very toxic OsO4, but the ring opening of the epoxide to the glycol is not trivial, because acidic conditions can not be used.

By the way, have you even bothered checking the literature for the known preparations of asarone to 2,4,5-trimethoxybenzaldehyde? Somehow it appears to me like you did not.

Methansaeuretier - 21-6-2010 at 03:30

Quote: Originally posted by Nicodem

Would'nt that mostly produce (in theory) phyenylacetone? All I want is the benzaldehyde, I'm not planning to make the amphetamine :mad:

forget your dirty thoughts![/rquote]
Oxidative cleavage of that glycol with metaperiodate gives the corresponding benzaldehyde (and not arylacetone as you seem to believe). Essentially, what Arrhenius proposed, is to prepare the glycol in separate steps followed by the usual oxidative cleavage with NaIO4 instead of doing the oxidation to the glycol and the cleavage to 2,4,5-trimethoxybenzaldehyde in one step like it is usually done (and requires OsO4 catalysis like in Chemistry Letters, 32, 780-781 or WO2002079132). This way you avoid the very toxic OsO4, but the ring opening of the epoxide to the glycol is not trivial, because acidic conditions can not be used.

Ah ok

makes sense thank you

Quote:

By the way, have you even bothered checking the literature for the known preparations of asarone to 2,4,5-trimethoxybenzaldehyde? Somehow it appears to me like you did not.

Well I don't have any literature... honestly all I was able to check was google and some e-books on my harddisk. I have no access to a libary at the moment. All interesting I found was some bad yielding KMnO4/NaHCO3 writeups on Rhodium and of course many others with derivates of this aldehyd, but all are working in acidic medium or with very hard obtainable reagents.

zed - 21-6-2010 at 21:13

Gotta be plans for some high yielding ozone generators hereabouts.

US Patent 2,916,499

http://www.google.com/patents?id=TQlMAAAAEBAJ&pg=PP1&...

[Edited on 22-6-2010 by zed]

[Edited on 22-6-2010 by zed]

Arrhenius - 21-6-2010 at 23:45

I would not suggest attempting ozonolysis unless you have good laboratory techniques and proper equipment. If reductive workup is not properly carried out, there's an excellent change you'll have an explosion. I haven't had this happen, but I have had other peroxides explode and it is not to be taken lightly.

The preparative workarounds for this is, as reiterated by Nicodem, are osmium catalyzed cleaveage, lead(IV) acetate cleavage or periodate cleavage. Because osmium is so incredibly toxic, it's frequently used catalytically with sodium periodate as a stoichiometric oxidant to re-oxidize osmium.

Yes, styrene oxides undergo facile rearrangement, but I have personally had a few open to the diol simply upon attempted chromatography on silica gel! You will always find papers that will convince you not to try an experiment, but it's often better to just give it a try and see for yourself or try to tweak things so they work for you.

Quote:

Even if you would isolate some epoxide, the rearrangement may produce similar pain. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi...

This article does not mention 70% yield of anything, but it does report 15% yield of the dimer you've drawn. Believe me, there are many many many ways you can make and isolate this particular epoxide.

Quote:

Well I don't have any literature..

Well read any published literature you can access. Read journal abstracts, supplementary information (free online) and open access journals such as Arkivoc

Quote:

All interesting I found was some bad yielding KMnO4/NaHCO3

Honestly, permanganate oxidations are seldom used for the sole reason that they're messy and poorly selective. Going from an alkene to a glycol with permanganate may be possible in the cold, but you'll probably have better success with other routes.

Epoxidation may also be possible using oxone. Here's a simple overview of the use of oxone to generate dimethyldioxiran (DMDO) in situ. Dioxiranes are highly effective at epoxidation, and are non-acidic. Oxone is commonly used as a "shock" treatment for pools, as you may already know.

[Edited on 22-6-2010 by Arrhenius]

zed - 22-6-2010 at 01:28

The above referenced patent, suggests that by ozonolysis, the target Benzaldehydes are produced directly. Without reduction.

Oxone is certainly a possibility. It's inexpensive, and easy to acquire. Yields might not be great, but its use doesn't entail the level of danger, that using either ozone or tetranitromethane would.

Methansaeuretier - 22-6-2010 at 04:57

Quote:

[quote=180607&tid=14038&author=zed]Gotta be plans for some high yielding ozone generators hereabouts.

US Patent 2,916,499

http://www.google.com/patents?id=TQlMAAAAEBAJ&pg=PP1&...

Thank you! Sounds very promising. I'll build an ozone generator next days and I'm going to try that.

Quote: Originally posted by Arrhenius

I would not suggest attempting ozonolysis unless you have good laboratory techniques and proper equipment. If reductive workup is not properly carried out, there's an excellent change you'll have an explosion. I haven't had this happen, but I have had other peroxides explode and it is not to be taken lightly.

I will try use cool methanol/H2O 9:1 as solvent and precipiate the product by addition of some water and strong cooling (asaraldehyde has melting point @ 111-115 ºC. Water solubility, <0.1 g/100 mL at 22 ºC), followed by recrist. from methanol. I don't see any dangers of explosions... or am I wrong?

Quote:

The preparative workarounds for this is, as reiterated by Nicodem, are osmium catalyzed cleaveage, lead(IV) acetate cleavage or periodate cleavage. Because osmium is so incredibly toxic, it's frequently used catalytically with sodium periodate as a stoichiometric oxidant to re-oxidize osmium.

Sounds nice, but I don't like to work with reagents like osmium, as long as it's not neccessary.

Quote:

This article does not mention 70% yield of anything, but it does report 15% yield of the dimer you've drawn. Believe me, there are many many many ways you can make and isolate this particular epoxide.

Yes, 15% of the dimer but 70% include the other stereoisomers of the dimer. And I know that there are other ways to the epoxide, but I don't know exactly how to get the aldehyde from the epoxide without exotic catalysts and acids.

Quote:

Well read any published literature you can access. Read journal abstracts, supplementary information (free online) and open access journals such as Arkivoc

Thank you, I didn't know Arkat. And btw. of course I read any interesting abstact and published literature I can find. But I wasn't able to find much about oxidation of styrenes to aldehydes under acid free conditions.

Quote:

Epoxidation may also be possible using oxone. Here's a simple overview of the use of oxone to generate dimethyldioxiran (DMDO) in situ. Dioxiranes are highly effective at epoxidation, and are non-acidic. Oxone is commonly used as a "shock" treatment for pools, as you may already know.

I know, DMDO dows work very nice (90%+ yields). But Oxone is hard to get in my country.
http://www.erowid.org/archive/rhodium/chemistry/safrolepoxid...
Even CH3CN/MeOH/Na2CO3/H2O2 does also work with 40% yields after destillation:
http://www.erowid.org/archive/rhodium/chemistry/epoxide.html
Also methyltrioctylammonium phosphoperoxotungstate may work as high yielding catalyst together H2O2 as oxidant
http://www.erowid.org/archive/rhodium/chemistry/peroxotungst...

Btw, asaroneepoxide is very unstable and has to be used directly.

As said my main problem is the reaction of the epoxide to the aldehyde. Do you have a writeup or something like that for that step?

BTW: Anyone ever tested dimeric/trimeric acetone peroxide instead of DMDO for this preparation? It's very easy to produce and isolate and as long it's kept very wet and washed neutral it's not very risky to use it. But illegal in some countries...

BTW in "Schulte-Ladbeck, R.; Kolla, P.; Karst, U. (2003). "Trace Analysis of Peroxide-Based Explosives". Analytical Chemistry 75 (4): 731–735" they also say that under neutral conditions H2O2 and Acetone produce "monomeric aceton peroxide" very slowly and the tetrameric (much more stable) derivate can be made if tin(IV)chloride and hydroquinone are used instead of a mineral acid. (Source: Jiang H., Chu G., Gong H., Qiao Q. (1999). "Tin Chloride Catalysed Oxidation of Acetone with Hydrogen Peroxide to Tetrameric Acetone Peroxide". Journal of Chemical Research 28: 288–289)"

[Edited on 22-6-2010 by Methansaeuretier]

[Edited on 22-6-2010 by Methansaeuretier]

leu - 22-6-2010 at 12:19

The most facile route to 2,4,5 trimethoxybenzaldehyde isn't from asarone because the work up is supposedly a royal pain in the ass but through vanillin, albeit acetic anhydride and bromine are necessary :cool:

[Edited on 22-6-2010 by leu]

gardenvariety - 22-6-2010 at 13:29

Quote: Originally posted by leu

The most facile route to 2,4,5 trimethoxybenzaldehyde isn't from asarone because the work up is supposedly a royal pain in the ass but through vanillin, albeit acetic anhydride and bromine are necessary :cool:

[Edited on 22-6-2010 by leu]

Procedures?

Just guessing, but acetylate the phenol, brominate ortho to the aldehyde, deacetylate the phenol to make the ring active to an Ullman?

Sandmeyer - 22-6-2010 at 14:12

Quote: Originally posted by gardenvariety

Procedures?

Just guessing, but acetylate the phenol, brominate ortho to the aldehyde, deacetylate the phenol to make the ring active to an Ullman?

A true gentleman would not protect/deprotect (in this case acetyl) if his desired substituent (in this case methoxy) can serve both as a directing as well as a protecting group.

gardenvariety - 22-6-2010 at 14:22

Quote: Originally posted by Sandmeyer

A true gentleman would not protect/deprotect (in this case acetyl) if his desired substituent (in this case methoxy) can serve both as a directing as well as a protecting group.

Wouldn't the unprotected phenol drive the position of the bromination? Most methods I have researched drive either para or ortho to the phenol; brominating at the 2 is meta to the phenol. That's why I guessed acetyl; as protecting it might allow bromination at the 2 and unprotecting it would allow for the Ullman, which is reportedly ineffective without a similarly strong EDG.

Aside from that, and aside from a meta-directing bromination, the only other route off the top of my head is methylation, oxidizing the aldehyde to phenol, then ortho-formylation and methylation in whichever order ones' reagents allow.

That doesn't require acetic anhydride, though, which is why I'm asking leu to explain.

Sandmeyer - 22-6-2010 at 14:29

Quote: Originally posted by gardenvariety

Quote: Originally posted by Sandmeyer

A true gentleman would not protect/deprotect (in this case acetyl) if his desired substituent (in this case methoxy) can serve both as a directing as well as a protecting group.

Ok. Methylation and subsequent bromination of vanillin should give you 6-bromoveratraldehyde, this can be Ullmanized...

edit:

Quote:

That's why I guessed acetyl; as protecting it might allow bromination at the 2 and unprotecting it would allow for the Ullman, which is reportedly ineffective without a similarly strong EDG.

Reportedly? Could you please post the ref./method? I have a french paper where they report a 50% yield Ullman methoxylation of ethylenedioxy analogue of 6-bromopiperonal, i.e 7-Bromo-2,3-dihydro-1,4-benzodioxin-6-carboxaldehyde, http://www.sciencedirect.com/science/article/B6THS-453BS8F-J... . The Frenchmen have no experimental in their letter but they do refer to the method in the paper http://www.erowid.org/archive/rhodium/chemistry/345-tmba.van... as the method they use for methoxylation, their 50% yield is rather low, but IMHO worth it if you can avoid resorting to protecting group. I'd like to see the report you mention.

[Edited on 22-6-2010 by Sandmeyer]

[Edited on 22-6-2010 by Sandmeyer]

gardenvariety - 22-6-2010 at 15:29

Quote: Originally posted by Sandmeyer

I didn't see a single paper out to disprove it, but rather commentary in 3 separate papers that found negligible yields on those substrates. I'll try to dig them up over the next few days, because it's been awhile.

All that aside, that still wouldn't require ac. anhydride. Still curious.

zed - 22-6-2010 at 17:57

Producing the desired material via 2,5-dimethoxy toluene, via bromination, might be possible. (If that toluene is available!)

Such a procedure is used industrially to produce 3,4,5-Trimethoxy benzaldehyde, from p-hydroxy-toluene .

Mono-Bromination of the aromatic ring....should proceed at the 4 position. Thereafter, followed by dibromination, of the toluel end of the molecule.

Treatment of the resultant 2, 5-dimethoxy-4-bromo- BenzalBromide. With Potassium methoxide, then might proceed to eventually produce the 2,4,5- trimethoxy-benzaldehyde.....

4-Bromination of the 2,5-dimethoxy benzyl- function....is well documented. This reaction has been used for the clandestine manufacture of DOB.

Others may have clearer insight into the possibility of using such a route. Asarone being pretty exotic; it may not be the best route for producing its own aldehyde.

Also, I don't know where you are located, but Oxone in some form is probably available. It's a common pool/jacuzzi chemical.
It's sometimes sold retail under the name trade Oxone, but more often, it is sold under a more generic name.

There are many threads on the subject of Oxone, buried in the archives.

[Edited on 23-6-2010 by zed]

[Edited on 23-6-2010 by zed]

[Edited on 23-6-2010 by zed]

[Edited on 23-6-2010 by zed]

Sandmeyer - 22-6-2010 at 20:21

No need to complicate, a gentleman makes this compound from OTC chemicals, namely from vanillin via methylation to veratraldehyde, Baeyer-Villager (peracetic i.e H2O2/AcOH), NaOH hydrolysis, metylation again to obtain 1,2,4-trimethoxybenzene, now, you use a sulfuric Ullmann variant of Duff formylation (see sticky thread). The substrate should be activated enough for this formylation if it does not work try to formylate the phenol and metylate as final step. All OTC...

Methansaeuretier - 23-6-2010 at 04:15

Thank you all!

Quote: Originally posted by Sandmeyer

No need to complicate, a gentleman makes this compound from OTC chemicals, namely from vanillin via methylation to veratraldehyde, Baeyer-Villager (peracetic i.e H2O2/AcOH), NaOH hydrolysis, metylation again to obtain 1,2,4-trimethoxybenzene, now, you use a sulfuric Ullmann variant of Duff formylation (see sticky thread). The substrate should be activated enough for this formylation if it does not work try to formylate the phenol and metylate as final step. All OTC...

What's your your prefered OTC methylation agent?

To go from 4-Bromo to 4-Methoxy via sodium methoxide sounds much more attractive to me, as theres no need of using highly toxic methylating agents.
I'll have a look around if 2,5-Dimethoxytoluene is available for me... bromination, methoxylation and oxiation to the aldehyde sounds pretty easy. Thank you zed.

Nicodem - 23-6-2010 at 04:47

You could have said already in the beginning that all you want is the product and spared us the ode to asarone. Why bothering us with questions about the oxidative cleavage of asarone if your problem is actually the preparation of 2,4,5-trimethoxybenzaldehyde by any means? BTW, are you aware that it is commercially available?

Quote: Originally posted by Methansaeuretier

To go from 4-Bromo to 4-Methoxy via sodium methoxide sounds much more attractive to me, as theres no need of using highly toxic methylating agents.
I'll have a look around if 2,5-Dimethoxytoluene is available for me... bromination, methoxylation and oxiation to the aldehyde sounds pretty easy. Thank you zed.

About 4-bromo-2,5-dimethoxytoluene and Ullmann: In comparison to the aldehyde or phenolic OH groups, the ortho-methoxy group is a very poor copper chelator and thus Ullmann condensations with o-haloanisoles in most cases do not perform well, unless very efficient external ligands are used. Exceptions are Ullmann condensations with tiolates and nucleophiles that themselves act as efficient Cu chelators.

About 6-bromoveratraldehyde and Ullmann: The aldehyde group is a moderately good copper chelator and thus the Ullmann condensations on such substrates (o-bromobenzaldehydes) do indeed work and there are relatively many examples in the literature (best ortho chelators for Cu are the COOH and NO2 groups, but phenolic OH is nearly as good). However practically all these examples use nucleophiles with lower basicity (phenoxides, thiolates...). The example given by Sandmeyer is practically the only one where a strongly basic nucleophile is used and this leads me to believe that the major problem here is the competition with the Cannizzaro reaction. While the deprotonated vanillin derivatives are notoriously stable in regard to the Cannizzaro reaction and the phenolic OH an excellent ortho-chelator for Cu, the same can not be said for the veratraldehydes and the aldehyde group.

In short, I think the Bayer-Villiger on veratraldehyde, O-methylation and Vilsmeier-Haack formylation as proposed by Sandmeyer is a more convenient and reliable route. Mainly because all the steps are already described in the literature, while the use of the Ullmann's sulfuric Duff formylation is a reasonably good and potentially working alternative to the Vilsmeier-Haack.

[Edited on 23/6/2010 by Nicodem]

Sandmeyer - 23-6-2010 at 04:53

Quote: Originally posted by Methansaeuretier

Obviously you are not even capable of opening the thread I mention, in which Ullmann discuss the preparation and use of OTC methylating agent as well as OTC formylation. Good luck with your endeavours, you'll need it...

Quote:

All I want is the benzaldehyde, I'm not planning to make the amphetamine :mad:

forget your dirty thoughts!

Yeah, right.

Methansaeuretier - 23-6-2010 at 09:34

Quote:

[quote=180718&tid=14038&author=Nicodem]You could have said already in the beginning that all you want is the product and spared us the ode to asarone. Why bothering us with questions about the oxidative cleavage of asarone if your problem is actually the preparation of 2,4,5-trimethoxybenzaldehyde by any means? BTW, are you aware that it is commercially available?

The product isn't all I want.
And I like to make it, not to buy it. The journey is the reward.

And I'll try the oxidative cleavage of asarone in any case, because I have about 100g of ~90 % asarone which only needs to be destilled once more and an ozone-generator is already ordered.
Anyhow the other way sounds also interesting, because I've never done something like that before.

BTW. 100g 2,4,5-Trimethoxybenzaldehyde from aldrich costs more than 140€. For 140 € I can buy at least 1100 ml of 45-80 % calamus oil and maybe produce more than 500 grams in one day.

Nicodem - 23-6-2010 at 09:53

Now that I think of it, the modified Duff formylation of 1,2,4-trimethoxybenzene should proceed already in plain acetic acid (without the sulfuric modification). At least this is the case with 1,3-dimethoxybenzene (UTFSE), which is only slightly more activated (it doesn't have the inductively deactivating and resonance non-participating MeO group of 1,2,4-trimethoxybenzene - the one that later becomes meta to -CHO).

The retro-Henry condensation mentioned by Zed is nice idea to test. The required 1-(2,4,5-trimethoxyphenyl)-2-nitropropene can be prepared by nitrosation of alpha- or beta-asarone following by treatment with a base.

Edit: The references for the vanillin=>veratraldehyde=>1,2,4-trimethoxybenzene route are Helvetica Chimica Acta, 47 (1964) 1996-2017 and Synthetic Communications, 39 (2009) 3693-3709.

[Edited on 23/6/2010 by Nicodem]

Sandmeyer - 23-6-2010 at 12:52

Quote: Originally posted by Nicodem

In short, I think the Bayer-Villiger on veratraldehyde, O-methylation and Vilsmeier-Haack formylation as proposed by Sandmeyer is a more convenient and reliable route.

[Edited on 23/6/2010 by Nicodem]

Nope, sorry, I never proposed Vilsmeier-Haack, since it is not OTC, I proposed OTC methylation, OTC Baeyer-Villager on veratraldehyde and OTC Duff formylation.

[Edited on 23-6-2010 by Sandmeyer]

Nicodem - 24-6-2010 at 00:50

Quote: Originally posted by Sandmeyer

Nope, sorry, I never proposed Vilsmeier-Haack, since it is not OTC, I proposed OTC methylation, OTC Baeyer-Villager on veratraldehyde and OTC Duff formylation.

Pardon. I had the route in mind rather than the specific reactions and methods. The thing is that Vilsmeier-Haack on 1,2,4-trimethoxybenzene is supported by several literature examples, while I was unable to find examples for the modified Duff. It might work with hexamine/AcOH though, but whether someone prefers OTC or OTS ("of the shelf") depends, not only on what is available in the local shops and on lab shelves, but also which method is already verified. Which is not to say that one should always chose the verified method. For example, I prefer to live on the edge and have a stressful life, so I often chose to check new methods.